Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND).
E van Weert, H J De Vuyst, Katleen van der Gucht, E Debbaut, J Steyaert, Kaat Alaerts
BMC Psychiatry July 1, 2025 DOI: 10.1186/s12888-025-07077-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 120 |
| Population | Adults with heightened stress complaints |
| Interventions | Oxytocin Mindfulness-based training |
| Duration | 6-week intervention, 6-week follow-up |
| Topics | Meditation |
| Keywords | Clinical trial Oxytocin Stress regulation Young adults |
| Key findings | The trial will test whether oxytocin combined with mindfulness training reduces stress, depression, and anxiety more than either intervention alone. |
Abstract
Oxytocin administration is increasingly considered a novel therapeutic support option for alleviating psychological distress in stress-related neuropsychiatric conditions, including anxiety disorders and depression. However, oxytocin as a stand-alone treatment may fail to consistently target the relevant central autonomic circuitry without a complementary supportive therapeutic context that similarly stimulates stress-regulatory states and behaviors. Recent findings suggest that the neurophysiological mechanisms underlying stress regulation induced by mindfulness may rely on an activation of the endogenous oxytocinergic system. Accordingly, combining oxytocin with a mindfulness-based training program may enhance efficacy compared to each intervention alone. A randomized, double-blind, placebo-controlled clinical trial will be conducted in 120 adults with heightened stress complaints, randomly assigned to one of the following four treatment arms (n = 30 per group): (1) oxytocin + mindfulness, (2) mindfulness + placebo, (3) oxytocin, and (4) placebo (control). The oxytocin or placebo nasal spray will be administered four times a week in the morning before each mindfulness session for six weeks, followed by a six-week post-treatment follow-up session. Primary endpoints include self-reported behavioral measures of stress, depression, and anxiety. Secondary endpoints include self-reported behavioral measures of mood, mindfulness skills, quality of life, sleep quality, and negative thinking. Exploratory measures include (i) electroencephalography (EEG), electrocardiography (ECG), skin conductance, and respiration, measured during rest, meditation, stress induction, and stress recovery; (ii) intervention-induced changes in biological samples, including hormonal levels of oxytocin and cortisol and DNA methylation of the oxytocin receptor gene (OXTR); and (iii) stress reactivity in daily life, assessed through experience sampling and heart rate/sleep monitoring. All outcome measures will be assessed at baseline (T0), immediately post-intervention (T1), and at six-week follow-up (T2). These findings could provide valuable insights into how combining oxytocin and mindfulness-based interventions might enhance stress regulation, particularly in populations with impaired oxytocinergic function. This trial was registered in the EU Clinical Trials Register (EU CT 2024-513482-39-00) on 18 March 2025.
Comparable studies
Other randomized controlled trials on meditation, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Alterations in Brain and Immune Function Produced by Mindfulness Meditation Healthy employees in a work environment | 2003 | Randomized controlled trial | n = 41 |
| Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. Recovered recurrently depressed patients | 2000 | Randomized controlled trial | n = 145 |
| Open hearts build lives: Positive emotions, induced through loving-kindness meditation, build consequential personal resources. Working adults | 2008 | Randomized controlled trial | n = 139 |
| Short-term meditation training improves attention and self-regulation Undergraduate Chinese students | 2007 | Randomized controlled trial | n = 40 |
| Mindfulness-Based Cognitive Therapy for Depression: Replication and Exploration of Differential Relapse Prevention Effects. Recovered recurrently depressed patients | 2004 | Randomized controlled trial | n = 73 |
Citations in the library
Cites 7
- The Empirical Status of Mindfulness-Based Interventions: A Systematic Review of 44 Meta-Analyses of Randomized Controlled Trials Perspectives on Psychological Science February 16, 2021
- A novel role of oxytocin: Oxytocin-induced well-being in humans Biophysics and Physicobiology 2019
- Target mechanisms of mindfulness-based programmes and practices: a scoping review. BMJ mental health August 24, 2024
- Oxytocin Modulation in Mindfulness-Based Pain Management for Chronic Pain. Life February 15, 2024
- Brief mindfulness session improves mood and increases salivary oxytocin in psychology students. Stress and Health October 1, 2020
and 2 more in the library